Egypt is the country with the highest prevalence of hepatitis C virus (HCV) infection worldwide with a nationwide prevalence of > 10% (compared to the USA prevalence of 2%) with an estimated 5 millions with chronic HCV infection. The morbidity and mortality of HCV is predominantly related to the development of significant fibrosis and cirrhosis inconspicuously in approximately 20% of chronically HCV patients. Current therapies with combined pegylated interferon are effective in 40- 50% of cases with genotype 4 in Egypt with better sustained virological response in early stages of fibrosis. The current US and Egyptian recommendations for the treatment of HCV suggest that patients have a liver biopsy to identify the most suitable patients for treatment with presence of evidence of fibrosis but before marked fibrosis develops. Liver biopsy is invasive and not readily available or accepted by all patients and is performed only when patients seek treatment. The development of an easily applicable and validated non-invasive system to stage liver fibrosis in patients with HCV would have many advantages including identification of progression of liver disease at early stages. The aim of this proposal is to develop in the US and then validate in Egypt a non-invasive staging system to identify patients with different stages of HCV related fibrosis and cirrhosis. This proposal has the potential to rapidly identify patients suitable for treatment and patients with advanced HCV related disease to rationalize treatment options and HCC screening in Egyptian communities. We will use the RO3 mechanism to explore the feasibility of performing a large scale screening program for liver fibrosis in Egyptian HCV patients. Specific Aim 1: To characterize and validate a panel of serum markers for monitoring of fibrosis progression in chronic hepatitis C infection. Specific aim 2: To establish the feasibility for non-Invasive screening for HCV related fibrosis in Egyptian Community Clinics. Specific Aim 3: To perform a cost effectiveness and compliance study for the impact of screening on health care costs and benefits in Egypt. Research design will include phase one of validation of a panel of markers in sera of more than 300 patients with paired biopsies to identify the optimal screening program to include serum liver tests, AFP, serum fibrosis markers. In phase two a screening program for chronic HCV patients will be established in community liver clinics to perform a cost effective screening program for liver fibrosis. [unreadable] [unreadable]